Abstract
The present study comprised sarcomeric genotyping of the three most commonly involved sarcomeric genes: MYBPC3, MYH7, and TNNT2 in 192 unrelated Egyptian hypertrophic cardiomyopathy (HCM) index patients. Mutations were detected in 40 % of cases. Presence of positive family history was significantly (p = 0.002) associated with a higher genetic positive yield (49/78, 62.8 %). The majority of the detected mutations in the three sarcomeric genes were novel (40/62, 65 %) and mostly private (47/62, 77 %). Single nucleotide substitution was the most frequently detected mutation type (51/62, 82 %). Over three quarters of these substitutions (21/27, 78 %) involved CpG dinucleotide sites and resulted from C > T or G > A transition in the three analyzed genes, highlighting the significance of CpG high mutability within the sarcomeric genes examined. This study could aid in global comparative studies in different ethnic populations and constitutes an important step in the evolution of the integrated clinical, translational, and basic science HCM program.
Highlights
Evaluation of genetic basis of inherited heart muscle disease is a prerequisite for further population, phenotypic, and mechanistic studies
The present study comprised sarcomeric (MYBPC3, MYH7, and TNNT2) genotyping of 199 consecutive unrelated Hypertrophic cardiomyopathy (HCM) index patients recruited from the different geographic regions of Egypt from July 2007 to June 2010 following standard clinical evaluation by 2D echocardiography at the satellite HCM clinics in Alexandria Faculty of Medicine, Cairo Faculty of Medicine, National Heart Institute, and Aswan Heart Center
The patient cohort comprised: 192 clinically diagnosed HCM patients, a single patient had left ventricular (LV) noncompaction cardiomyopathy without hypertrophy (P76), and six patients were clinically suspected as HCM phenocopies: five patients were suspected to be infiltrative due to storage disease based on symmetrical hypertrophy and highly reflective myocardium and/or presence of history of parental consanguinity and presence of horizontal transmission pattern and one patient was suspected to have mitochondrial cardiomyopathy due to associated bilateral optic neuritis
Summary
Evaluation of genetic basis of inherited heart muscle disease is a prerequisite for further population, phenotypic, and mechanistic studies. Hypertrophic cardiomyopathy (HCM) is a model of common genetic heart disease attracting the interest of cardiologists, geneticists, scientists, and the public. Different population studies reported the prevalence of HCM, based on left ventricular (LV) wall thickness greater than 15 mm, as 1:500 (0.2 %) [2, 3]. This frequency represents the tip of the iceberg and is probably an underestimate since it represents only the clinically manifest HCM and does not include the prehypertrophic stage represented by the genotype-positive/phenotype-negative cases [4]. Based on the reported prevalence in different populations, an estimate of at least 160,000 individuals is expected to be affected with HCM within the over 80 million population of Egypt [5]
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